I propose it may be from a comorbid infection of Streptomyces ( not sure which strain yet,) B. thetaiotaomicron, and Prevotella. The different forms
may also be attributable to different combinations of similar species, such as Bacteroides, such as Bacteroides fragilis, and also these conditions
seem related to Tannerella forsythia presence as well.
There may be a pathogenic component, especially considering Streptomyces is capable of horizontal gene transfer induction.
"Amongst N-acetylhexosaminidase inhibitors (Figure 1), 2-acetamido-1,2-dideoxynojirimycin, 1  and diastereomers such as the d-galacto (2)  and
the d-allo (3)  analogs, PUGNAc (4) , and NAG-thiazoline (NGT, 5)  have attracted considerable attention. Furthermore, Thiamet G (6) ,
nagstatin (7) , and 6-acetamido-6-deoxycastanospermine (8) , various pyrrolidine derivatives (for example, compound 9 ), as well as
2-N-acetyl glycals including 10  have been reported. Amongst carbacyclic hexosaminidase inhibitors, pyranoid carbasugar
acetamidodeoxy-β-valienamine (11) has to be mentioned . These inhibitors are either substrate/product analogs or, in the case of bicyclic systems
such as NGT, are chemically stable structural analogues of the above-mentioned intermediate generated by anchimeric assistance of the N-acetyl group
at C-1 at the first transition state of enzymatic N-acetylhexosaminide hydrolysis. "
"Streptomyces plicatus by 2-acetamino-1,2-dideoxynojirimycin-lysine hybrids"
"Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase (NAG-ase) was discovered in the fermentation broth of Streptomyces amakusaensis
MG846-fF3. It was purified by chromatography on Dowex 50W, Avicel and Sephadex LH-20 followed by the treatment of active carbon and then isolated as
colorless powder. Nagstatin has the molecular formula of C12H17N3O6. It is competitive with the substrate, and the inhibition constant (Ki) was 1.7 x
10(-8) M. "
We report here the identification, characterization, purification, cloning, and expression of a novel enzyme that is able to remove sulfate from mucin
oligosaccharide chains by glycosidic cleavage of terminal 6-SO3-β-GlcNAc residues. The enzyme was found in Prevotella strain RS2, an anaerobic
bacterium originally isolated from pig colon mucosa. We termed this enzyme a sulfoglycosidase and showed that it differs from the mucin-desulfating
sulfatase, MdsA, that has been described previously. The SGL activity is not due to sequential action of MdsA and hexosaminidase. SGL is translocated
to the periplasm, as shown by cell fractionation studies and by the presence of a periplasmic translocation motif at the N terminus of the translated
product. At least one other fraction catalyzing SGL activity was detected during purification, and we have not investigated yet whether this fraction
is a degradation product of the 100-kDa protein or is an isoenzyme.
SGL was tested for activity against a number of model substrates which have structures analogous to the structures of sugars in mucin oligosaccharide
chains (Table (Table2).2). Activity was found only with 6-SO3-β-GlcNAc-1-pNP, in agreement with data showing that SGL released free 6-SO3-GlcNAc from
mucin. The inability of SGL to cleave pNP from the disaccharide substrate 4-(β-Gal)-6-SO3-β-GlcNAc-1-pNP strongly suggests that the enzyme is an
When the translated 901-amino-acid sequence (before translocation of the SGL) was compared with BLAST protein database sequences, the closest matches
were with β-hexosaminidases from B. thetaiotaomicron and Porphyromonas gingivalis. To the best of our knowledge, these enzymes have not been isolated
and/or have not been tested for activity against sulfated substrates, and SGL activity has not been described previously in bacteria. When crude cell
extracts from several common species of gut anaerobes were assayed for SGL-like activity, B. fragilis and B. thetaiotaomicron appeared to have some
activity, although the levels were lower than the levels for Prevotella strain RS2. The possible activity detected in P. melaninogenica was most
likely due to sulfatase plus hexosaminidase. The nine other isolates tested had no SGL-like activity. It seems likely that some of the uncharacterized
members of the CAZy GH20 family may well catalyze SGL-type reactions rather than conventional β-N-acetylhexosaminidase reactions.
Only one other enzyme, human β-d-N-acetylhexosaminidase A, has been shown to remove intact 6-SO3-GlcNAc from 6-SO3-β-GlcNAc-1-pNP. Consistent with
this specificity, the human enzyme can liberate 6-SO3-GlcNAc from the nonreducing end of keratan sulfate-derived oligosaccharides. The enzyme can also
remove GlcNAc from β-GlcNAc-1-pNP and shows 20-fold-higher affinity for the nonsulfated substrate (10). In contrast, the Prevotella SGL cleaves the
nonsulfated substrate at a rate that is only 1% of the rate seen with the sulfated substrate (with substrate at a concentration of 1 mM), and the
difference is due to the fact that the nonsulfated substrate has a higher Km and a lower Vmax. The Km and Vmax values are for model substrates,
however, and may not necessarily be correct for native substrates. The Prevotella enzyme has a sevenfold-higher affinity (Km = 0.18 mM) for
6-SO3-β-GlcNAc-1-pNP than the human enzyme has. We have not tested the Prevotella SGL with keratan sulfate-derived oligosaccharides.
The human β-d-N-acetylhexosaminidase A is better known for its alternative specificity in cleaving N-acetylgalactosamine from the oligosaccharide
chain of GM2 ganglioside. The human recessive lysozomal storage disease (GM2 gangliosidosis) called Tay-Sachs disease (9) results from
β-d-N-acetylhexosaminidase A deficiency due to inheritance of mutant forms.
The finding that both a mucin-desulfating sulfatase (MdsA) (28) and SGL are present in the periplasm of Prevotella strain RS2 (and perhaps other
bacteria) leads us to propose that sulfate group metabolism in sulfomucins, sulfoglycoproteins, and/or sulfoglycolipids must have important functions
in the colonic habitat, which the bacterium is attempting to modify. These enzymes may enhance the ability of the bacterium to survive in its
environment. Both enzymes are partially induced by growth on mucin, and both can desulfate mucin. The product of SGL action is a substrate for MdsA
sulfatase, but not vice versa. The proposed roles of SGL in mucin metabolism may be hypothesized to be (i) removal of inhibitory 6-SO3-β-GlcNAc
groups from mucin chains that limit degradation of the chain by exoglycosidases and neuraminidases, (ii) removal of 6-SO3-β-GlcNAc groups from mucin
chains (usually exposing a galactose as the new terminal residue), thus creating or removing sites for different adhesins, and (iii) provision of
6-SO3-GlcNAc as a readily hydrolysable substrate for MdsA sulfatase. The first two roles could have substantial effects on the colon mucosal
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